Mental Health Award: understanding how interventions for anxiety, depression, and psychosis work

Mental Health Award: understanding how interventions for anxiety, depression, and psychosis work is sponsored by Wellcome Trust. This call provides funding for teams of researchers working across any discipline of relevance to mental health science.

### This scheme is now closed Lead applicant career stage:Funding amount: * You should ask for the resources that you need and are appropriate for your proposed research project, justifying these costs in your full application. See the 'What we offer' section on this page.

Up to 8 years but can be much shorter ##### CLOSED TO NEW APPLICATIONS As part of our new strategic focus on mental health as a key global health challenge, Wellcome aims to develop new and improved early interventions for anxiety, depression and psychosis, in ways that reflect the priorities and needs of people experiencing these conditions.

This work involves increasing scientific understanding of how brain, body and environment interact in the development and resolution of these problems. This call focuses on investigating the causal mechanisms underpinning the active ingredients of effective interventions for anxiety, depression and/or psychosis.

By active ingredients, we mean those aspects of an intervention that: * drive resolution or reduction of symptoms * are conceptually well defined * link to specific hypothesised mechanisms of action.

Active ingredients are diverse and wide-ranging, including: * biological (for example, sleep-wake cycles, reduced inflammation in the body, selective serotonin reuptake inhibitors) * cognitive (for example, emotion regulation, mental imagery, reduced repetitive negative thinking) * behavioural (for example, behavioural activation, exposure, physical activity) * relational (for example, peer support, social relationships, working alliance) * societal (for example, social inclusion, urban access to green space).

Since 2020, Wellcome has been considering different routes to resolution. We commissioned 51 teams to identify and review the evidence for more than 40 active ingredients. Teams were asked to consider ‘what works, for whom, in what contexts, and why’, with a particular focus on youth anxiety and/or depression.

Looking across the reviews, a clear gap emerged: while there is evidence to show that many active ingredients are effective, we know much less about the biological, psychological, and social mechanisms of action underpinning how and why these ingredients work.

It also became clear that there is currently not enough research being done across different disciplines and levels of explanation (for example, molecular, cellular, circuits, systems, behaviour, or societal levels) to provide the information we need to identify causal mechanisms.

This is crucial because, just as the causes of mental health problems involve a tangle of biological, psychological, and social factors, so too do the solutions. Illuminating the relationship between these different aspects may be key.

Without the mechanistic understanding of how and why active ingredients work, it is much more difficult to develop new and improved early interventions and to target them to the right people at the right time. This funding call proposes to address this gap in our understanding.

We strongly recommend applicants read the report summarising the first 30 commissioned reviews, to help them understand what we mean by the concept of active ingredients and the sort of evidence being considered. But please note that the present funding call has a broader scope.

While the report focuses on anxiety and depression in 14-24-year-olds, the present funding call also considers psychosis and is not limited to a particular age group, provided the focus is on intervening as early as possible. We are aware this may vary by context, and so age will not be a cut-off in itself.

We also acknowledge that research seeking to understand how interventions work in older groups may serve to improve options for early intervention further down the line. In all cases, applicants must justify the relevance of their proposal for improving prospects for prevention or intervention at an early stage.

For more information on Wellcome’s approach to active ingredients, including relevant publications by our team and the researchers we commissioned, please see the ‘Useful documents’ section on this page. You can apply for this Mental Health Award if you are a team of researchers who propose to investigate the causal mechanisms underpinning the active ingredients of effective mental health interventions.

An intervention may be: * something that an individual can do themselves * something provided by a healthcare professional * something provided by communities and wider civil society. By taking a back (or reverse) translation approach, we will fund projects that start with one (or more) effective active ingredient(s) and work backwards from the evidence to understand why/how the chosen ingredient(s) works.

The insights gained through this work will (either directly or in time) inform the development of new and improved early interventions. This should involve research projects that will advance knowledge in relation to any of the following:​ * How a single putative mechanism at one or more levels of explanation (for example, molecular, cellular, systems, or societal levels) plays a causal role in the resolution of problems​.

* How different mechanisms (for example, biological, psychological, or social) interact in the resolution of problems​.

In addition to addressing the above, projects may also explore, for example: * how different contexts impact on the efficacy and/or effectiveness of the active ingredient(s) under investigation * identification and/or validation of markers (whether biological, psychological, social, or mixed) that can predict whether an individual will respond to a specific active ingredient(s). #### What are we looking for?

* We are interested in understanding the causal mechanisms underpinning the active ingredients of effective early interventions for anxiety, depression, and/or psychosis.

* We take anxiety, depression, and psychotic disorders as broadly defined categorisations to include all types of anxiety and depressive disorders (including obsessive compulsive disorder and post-traumatic stress disorder) and all forms of psychotic disorders (including schizophrenia, postpartum psychosis, and bipolar disorder).

* We recognise that the current diagnostic categories are imperfect but removing all categories or creating new ones also presents difficulties. Therefore, we propose to keep using these as broadly defined constellations of features or symptoms. We take anxiety, depression, and psychosis to refer to constellations of thoughts, feelings, and behaviours that have historically been classified as discrete conditions.

Active ingredients of particular interventions are in scope if they are aimed either at the level of the diagnostic category, or if they address specific distressing and impairing symptoms, thoughts, feelings, or behaviours broadly defined as part of anxiety, depression, and/or psychosis.

Whilst we do not specify any particular diagnostic or classificatory system, we expect applicants to utilise a framework and measurement approach that fits the aim of their study, and to provide a clear rationale for doing so.

* The research question proposed must have sufficient scope and ambition, such that the findings have the potential to transform early intervention options for people with anxiety, depression and/or psychosis (either directly or in time). * You can choose to investigate one of ourpreviously studied active ingredients or propose a new active ingredient. You must justify your choice.

* You can focus on a single active ingredient or on the interaction between multiple active ingredients, provided the focus of your proposal is on advancing understanding of how and why they work (what are their causal mechanisms, either in isolation or combination).

* The proposed active ingredient(s) must be clearly defined and grounded in evidence, meaning that it must already have been shown to be effective in people with anxiety, depression, and/or psychosis.

* By effective we mean: (i) the active ingredient, or (ii) the intervention of which the active ingredient is hypothesised to be a part, has been shown to cause a significant positive change on a validated measure relevant for anxiety, depression, or psychosis in a defined population. Ideally this should be shown in at least one peer-reviewed (and preferably pre-registered) randomised control trial.

The applicant should justify their choice based on the strength of the evidence and discussion of effect size. * You must suggest a potential mechanism (or mechanisms) of action for your chosen active ingredient(s) and use experimental approaches that will provide causal (rather than correlative) evidence to support/disprove that mechanism.

* Applications must demonstrate the involvement of lived experience expertise in the planning, design, and delivery of the research. We recognise that there are a range of ways that research teams can involve and collaborate with people with lived experience. For example, this may include, but not be limited to, expert advisors, co-applicants, collaborators, or advisory group members.

We are open to any methods of involvement that teams choose but expect lived experience experts to be involved in the most appropriate ways to inform multiple aspects and stages of the research project. Key for us is that this is not tokenistic or a tick box exercise. * For further information on what we mean by ‘people with lived experience’, including guidance for meaningful involvement, see the supplementary material provided.

* You should use the most appropriate methodologies to address your research question. These may include (but is not limited to) experimental, computational modelling, and/or trials approaches, and may involve human and/or model systems (for example animal, cellular) as appropriate.

* Where projects explore active ingredients targeting anxiety and/or depression, teams conducting research projects with human participants must use (as a minimum) one or more of our recommended common measures for anxiety and depression.

This means using a version of one or more of the following (preferred version in brackets), where possible: * For depression, the Patient Health Questionnaire for Depression (PHQ-9) * For anxiety, the General Anxiety Disorder Assessment for Anxiety (GAD-7) * For youth anxiety or depression, the Revised Child Anxiety and Depression Scale (RCADS-25) * For general health and impairment, The WHO Disability Assessment Schedule 2.

0 (WHODAS 2. 0) * In exceptional circumstances when these measures are not feasible (for example, due to length), we may agree to the use of shorter versions (for example, PHQ-2, GAD-2, RCADS-10). However, the reasoning for this must be clearly justified.

In addition to using the recommended measures, we strongly encourage applicants to supplement these measures with other data collection tools, as appropriate. Please note that we do not currently have an agreed measure for psychosis, therefore, applicants should use the measure(s) that is most appropriate to address their research question. #### What are we not looking for?

The following are**out of scope** for this Mental Health Award: * Studies exploring neurodevelopmental conditions, neurodegenerative diseases, or mental health problems outside of anxiety, depression, and/or psychosis (for example eating disorders, substance abuse). * Universal (population-level) preventative interventions and/or interventions focused on managing chronic mental health problems.

* Suicide, self-harm and reducing stigma are out of scope as broad outcomes in themselves. However, interventions that target suicide/suicidal ideation, self-harm and reducing stigma as a means of reducing symptoms of depression, anxiety or psychosis as primary outcomes would be in scope.

* Projects studying the mechanisms of interventions for which there is no or limited evidence, and by extension proposals to develop and test new interventions. * ‘Blue-skies’ or curiosity-driven research. * Research into the effectiveness and/or efficacy of untested active ingredients.

* Projects that do not include the involvement of lived experience experts in the proposed project unless justified. We are interested in receiving applications from a range of geographies, including low- and middle-income countries. We also want to see applications from the full breadth of mental health science, and we especially encourage those from diverse and multidisciplinary teams.

Our definition of mental health science includes, but is not limited to: * cellular and molecular sciences * circuit, systems, and cognitive neurosciences * disciplines within the humanities, social sciences, and computer sciences (for example, anthropology, sociology, geography, law, political science, economics, informatics) * lived experience expertise, which is explicitly recognised as central to mental health science.

#### About you (Lead applicant) * have experience directly relevant to the proposed project, as evidenced through research outputs and/or preliminary data (as appropriate for your career stage) * be able to drive and lead a collaborative, multi-stranded health-based research project (as appropriate for your career stage) * be able to contribute at least 20% of your research time to this project.

As the lead applicant you will have a PhD (or equivalent) with significant postdoctoral research experience and will already be leading your own independent research programme. You can only submit one application as ‘lead applicant’ to this call. You can be included as a co-applicant on other applications to Wellcome or hold other Wellcome awards but must demonstrate that you have sufficient capacity for the project if funded.

See 'who can’t apply' below for more detail. * higher education institution * non-academic healthcare organisation * not-for-profit organisation At the point of application, you should have a permanent, open-ended, or long-term rolling contract, or the guarantee of one. The contract should not be conditional on receiving this award.

Your salary should be paid by your host organisation for the duration of the award, however if this is a condition of your employment contract, salary may be requested. If you have less than three years remaining on your contract at the point of application (and your contract will finish before the proposed project end date), you must have secured your next position at an eligible organisation and provide a letter of support from them.

In alignment with Wellcome’s grant conditions, foreground intellectual property (IP) is owned by the lead applicants’ host organisation. In addition, the awardee must commit to publishing the data generated on the active ingredient(s), or otherwise using such data for public (rather than private) benefit.

So, if working in collaboration with a company (especially a company owning a specific relevant intervention, compound, or technique), you should discuss and agree these principles with them before applying and you will need to provide us with a copy of your collaboration agreement in due course.

#### About your co-applicants * Must have expertise that is essential for the delivery of the project, with their contribution to the project clearly justified. * Must have the appropriate time and necessary resources available to deliver the project. * Can be at any career stage and based anywhere in the world (apart from mainland China).

* higher education institution * non-academic healthcare organisation * not-for-profit organisation * Does not need to have a permanent, open-ended, or long-term rolling contract. They may be employed on another grant or ask for their salary on this application.

However, their employing host organisation must guarantee space and salary support (if they can’t get it from other sources) for the period of time that the co-applicant is working on the grant. * Can be based in the same or in different organisations, and come from any discipline, but the added value of their contribution to the project must be clear.

You may also want to consider involving people with lived experience of anxiety, depression, and/or psychosis (as appropriate) to be included in the project team, as co-applicants or collaborators. There are other ways of involving people with lived experience, and we would encourage you to review the supplementary material.

Collaborators are distinct from co-applicants in that they will support the delivery of the project (for example, providing technical or knowledge area expertise, access to tools or resources) but are not leading on a specific work-package or research aim of the project. Your team should be comprised of all the necessary expertise to support the research project.

This must include the necessary expertise to effectively involve and collaborate with people with lived experience of anxiety, depression and/or psychosis in the proposed project. We encourage lead applicants to put together diverse and multidisciplinary teams. You will be expected to actively promote a diverse, inclusive, and supportive research environment within your team and across your organisation.

Team size will depend on the proposed research. It will usually range from two to eight applicants, including the lead applicant,but we can be flexible if larger teams are required and justified. Team composition, including who the lead applicant is, cannot change between the preliminary and full application stage, unless this has been agreed with Wellcome in advance.

#### Time spent away from research You can apply if you've been away from research (for example, career break, maternity leave, long-term sick leave). We'll take this into consideration when we review your application. If you have retired, please contact us before applying.

Lead and co-applicants can be part-time. There is no formal minimum, but part-time working needs to be compatible with delivering the project successfully. #### What's expected of your host organisation We expect organisations based in the UK to meet the responsibilities required by the Concordat to Support the Career Development of Researchers for institutions, managers and researchers.

Any organisation with Wellcome funding that is based outside the UK is expected, at a minimum, to follow the principles of the Concordat. We also expect your host organisation to: * Guarantee that the space and resources you need have been agreed and will be made available to you from the start date through to the end date of your award. * Explain how your research fits with the strategic aims of the organisation.

* Give you, and any staff employed on the grant, 10 days a year (pro rata if part-time) to undertake training and continuing professional development (CPD) in line with the Concordat. This should include the responsible conduct of research, research leadership, people management, diversity and inclusion, and the promotion of a healthy research culture.

* Provide a system of onboarding, embedding, and planning for you when you join the organisation and/or start the award. * Provide you with the status and benefits of other staff of similar seniority.

If your host organisation is a core-funded research organisation (that is, if your organisation receives funding for its core facilities such as communications, governance, senior management salaries, etc.) a Mental Health Award should not replace or lead to your organisation receiving less from the core funds on those activities.

You cannot apply if you intend to carry out activities that involve the transfer of grant funds into mainland China or a country that is the target of international sanctions. You can only be an applicant on a maximum of two applications to this funding call: * You can only be lead applicant on one application (but can be a co-applicant on another).

* You must be able to demonstrate that you can dedicate enough time and resources to both projects, if funded. * An early-career researcher can be a lead applicant on one Wellcome award and a co-applicant on one other Wellcome award. * A mid-career researcher can be a lead applicant on one Wellcome award and a co-applicant on two other Wellcome awards.

* An established researcher can be a lead applicant on two Wellcome awards, one as the sole applicant and one as lead applicant for a team, or both as the lead applicant for a team. They can also be a co-applicant on two other Wellcome awards. The awards should be for different research projects, with no overlap in work packages.

The researcher must be able to dedicate the required time to all projects. Information on other open calls from the Mental Health team can be found on the team’s webpage. For completeness and for applicants’ planning purposes we provide below the full assessment criteria and weightings that will be used at the full application stage.

At the preliminary application stage, a simplified rubric will be used. For guidance on how to write your preliminary application, please see the ‘how to apply’ section.

The full assessment criteria is as follows: * Research question(s) and strength of proposed methodology (40%) * Suitability and expertise of the team (20%) * Lived experience involvement (20%) * Suitability of research location, environment, and culture (20%) Alongside the individual assessment criteria set out below, we will also consider portfolio-level criteria.

This will ensure that we build a diverse portfolio of funded projects, maximising the impact of this Mental Health Award. For example, ensuring we have a breadth of active ingredients and methodological approaches represented.

#### Research question(s) and strength of proposed methodology (40%)​ * The proposed research project must lead to insights into the causal mechanisms underpinning the impact of the active ingredient(s) under investigation, which could (either directly or in time) inform the development of new and improved early interventions for anxiety, depression and/or psychosis.

​ * The research question must have sufficient scope and ambition, such that the findings have the potential to transform early intervention options for people with anxiety, depression and/or psychosis.

To elaborate on what this could involve, the research project will advance knowledge in relation to any of the following: * How a single putative mechanism at one or more levels of explanation (for example, molecular, cellular, systems, or societal levels) plays a causal role in the resolution of problems​. * How different mechanisms (for example, biological, psychological, or social) interact in the resolution of problems​.

In addition to addressing the above, projects may also explore, for example: * How different contexts impact on the efficacy and/or effectiveness of the active ingredient(s) under investigation . * Identification and/or validation of markers (whether biological, psychological, social, or mixed) that can predict whether an individual will respond to a specific active ingredient(s).

​ Rationale and strength of evidence​: * The proposed active ingredient(s) is clearly defined and grounded in strong evidence, supporting its effectiveness and/or efficacy and applicability in people with anxiety, depression, and/or psychosis. ​ * A mechanism of action for the selected active ingredient(s) is clearly hypothesised and supported by evidence (for example, preliminary data, published literature).

​ Strength of proposed methodology​: * There is a clear project plan that addresses the hypothesis/research question, seeking to gain causal (rather than correlative) insights. ​ * In projects where a clinical trial/experimental medicine approach is used, the outcomes must primarily inform our understanding of causal mechanisms underpinning the impact of the active ingredient(s).

* The proposed methodological approach is appropriate, well-designed, feasible, and supported by relevant evidence or expertise (for example, the choice of model system is justified, the sample is adequately powered, for human studies a recruitment plan is in place, participant heterogeneity is being harnessed and/or considered in the study design). ​ * The project is achievable in the timelines proposed.

​ * The resources requested are appropriate and well justified. ​ #### Suitability and expertise of the team (20%)​ * Has research experience relevant to the project, as evidenced through research outputs and/or preliminary data (as appropriate for their career stage). ​ * Has the ability (or potential) to drive and lead a collaborative, multi-stranded health-based research project (as appropriate for their career stage).

​ * Can contribute at least 20% of their research time to this project. ​ * The co-applicants’ expertise is essential for the delivery of the project and their contribution to the project is justified. ​ * The co-applicants have the appropriate time and necessary resources available to deliver the project.

​ * The team has the necessary expertise and technical skills to deliver the proposed research project.

* There is a justified team approach whereby all applicants are necessary to deliver the proposed research, and there is proof of concept that the proposed collaboration would be feasible and fruitful (for example, the team has appropriate management plans in place, describing how the collaboration will be organised and run day-to-day).

* The team has the necessary expertise and skills to effectively involve and collaborate with people with lived experience of anxiety, depression and/or psychosis in the proposed project. * Applicants have contributed and are committed to fostering a positive and inclusive research culture.

#### Lived experience involvement (20%)​ * People with lived experience of anxiety, depression and/or psychosis (as relevant) are involved in multiple stages of the design, delivery, and dissemination of the project. * Approaches to involvement (or lack of involvement) at each stage of the project should be explained in detail. * People with lived experience are appropriately compensated or paid for their time.

* The involvement of people with lived experience is appropriately costed and budgeted. #### Suitability of research location, environment, and culture (20%)​ Taking into consideration the local context and setting we will review: Research location and environment * The research environment is suitable to support and develop the applicants and their proposed research.

​ * The host organisation is supportive of the research project (for example, it aligns with their strategy, they may provide in-kind or financial support in the form of PhD students, refurbed lab space, administrative/technical support, training opportunities). ​ * The applicants have access to the necessary research infrastructure.

​ * Detailed description of how the team will contribute to and develop a positive and inclusive research culture. This may (but is not limited to) include:​ * Project management plans, including how project priorities and decisions will be determined​. * Equitable plans for collaborating with researchers in low resource settings​.

* Plans for how contributions to research outputs will be credited as appropriate. * Plans for leadership and people management or development, supporting collaborations, research integrity and contributions to the wider research community. ​ Open research and data management plans​ * Detailed description of a suitable outputs management plan (for example, depositing, sharing and storing data, open access publishing).

* Duration of award: projects of any duration up to 8 years. * Level of funding: projects of any budget up to £5 million. There is no average award amount for this call.

You should ask for the level and duration of funding that is required to address your research question. You must justify all costs within the costs section of your application. You usually cannot ask for your salary.

However, you can ask for a contribution to your salary if you hold a permanent, open-ended or long-term rolling contract that states that you have to get your salary from external grant funding. The amount we pay will be proportionate to the time you contribute to the award, for example if you contribute 30% of your time to the award we will fund 30% of your salary.

You will have to contribute at least 20% of your research time to this award. Your host organisation must confirm: * that your employment contract states you must get salary recovery from external grant funding * that they will underwrite the salary and post for the period of time that you will be working on the grant. You can ask us for a contribution to their salary in your application.

The amount we pay will be proportionate to the time they contribute to the award, for example if they contribute 30% of their time to the award we will fund 30% of their salary. They will have to contribute at least 10% of their research time to this programme.

Your host organisation must confirm: * that the co-applicant’s employment contract states they must get salary recovery from external grant funding * that they will underwrite the salary and post for the period of time that the person will be working on the grant. #### Staff working on your programme We will cover the salary costs of all staff, full or part-time, who will work on your grant.

Staff members may include: * research assistants or technicians employed on your grant * experts with lived experience * specialist service staff, for example data analysis, fieldwork and clinical studies * project manager, if you have multiple applicants on your programme * support if you or a member of staff employed on your grant is disabled or has a long-term health condition – see 'Disability-related adjustment support'.

If you’re a humanities and social science researcher, you can ask for funds for research or teaching replacement to cover the cost of a temporary replacement lecturer. You must retain at least a 10% commitment to teaching. * can cover up to 33% FTE of your contracted time * are usually for a person at a more junior level than the postholder * can be spread across the full period of the grant.

If you already get buyout costs from another grant (funded by Wellcome or elsewhere), you can ask us for this cost, but only for the period of time on your Mental Health Award when you won't receive buyout costs from another grant. You must provide a letter from your employing organisation, confirming that your contract includes a teaching commitment. You should include this in your grant application.

We do not provide studentships on this award. But if applicants employ a research assistant on the grant, they can ask for the costs to cover their PhD fees. Each applicant can ask for PhD fees for one research assistant at a time on the grant.

We will only pay the international student fee rate for low- and middle-income nationals who are registered to study for a PhD in a high-income country. In all other situations, we will pay home student fees. Staff salaries should be appropriate to skills, responsibilities and expertise.

You should ask your host organisation to use their salary scales to calculate these costs, which should include: * employer’s contributions, including any statutory obligations (for example, National Insurance contributions if you’re based in the UK) and pension scheme costs * Apprentice Levy charges for UK-based salaries * any incremental progression up the salary scale * locally recognised allowances such as London allowance.

You should allow for salary pay awards during Year 1. If the pay award is not yet known, applicants should use the International Monetary Fund inflation rate, selecting the ‘inflation, average consumer price’ option as an indicator. From Year 2 onwards, you should use your organisation’s current pay rates.

We’ll provide a separate inflation allowance for salary inflation costs. Read about the responsibilities of grantholders and host organisations for people working on a Wellcome grant. If you have named people on your grant whose salaries will be funded by Wellcome, you can ask for visa or work permit costs to help them take up their posts at the host organisation.

You can also ask for: * visa costs for the person's partner and dependent children * essential associated costs, such as travel to attend appointments at a visa application centre or embassy if you can justify these * where